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Focal adhesion proteins promote cell adhesion and migration in both two-dimensional and three-dimensional environments. When cells are embedded in a 3D matrix, focal adhesion proteins modulate the speed and persistence of migration by regulating protrusion activity.
Morphogens direct cell fates across tissues through concentration gradients. Pentagone, a secreted protein and a newly identified target of the Drosophila bone morphogenetic protein decapentaplegic (Dpp), is shown to promote long-range distribution of the Dpp ligand in the wing through its binding to the heparan-sulphate proteoglycan Dally.
Viral infection is shown to trigger CREB-mediated upregulation of miR-132. The interferon response is then downregulated by miR-132 through direct targeting of p300, a transcriptional co-activator, thereby facilitating viral replication.
The cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in dynamic environments, such as the lung. CFTR is known to be activated by ligand binding. Here, it is also found to be activated by mechanical stretching of cellular membranes.
Rho guanine nucleotide dissociation inhibitors (RhoGDIs) bind to inactive Rho GTPases in the cytosol, but their function remains unclear. Several Rho GTPases are now shown to compete for RhoGDI binding and this is crucial for regulating Rho GTPase turnover and activation.
GEMC1 is a newly discovered protein required for initiation of DNA replication in Xenopus. xGEMC1 interacts with the replication factors TopBP1 and Cdk2 and promotes TopBP1- and Cdk2-dependent loading of Cdc45 onto replication origins.
Before meiosis II, centromeric sister chromatid cohesion is protected by shugoshin and protein phosphatase 2A, but the identity of the antagonising kinase has remained unclear. Casein kinase 1 is found to phosphorylate cohesin to promote its cleavage during fission yeast meiosis.
The DNA-damage checkpoint kinase Chk2 is a candidate tumour suppressor. Independently of DNA damage, Chk2 regulates spindle assembly and maintenance of chromosomal stability through phosphorylation of BRCA1.
Several recent studies have proposed that the planar cell polarity pathway (PCP) regulates cilia formation. Zebrafish embryos lacking the core PCP component Vangl2 do not have defects in ciliogenesis, but instead show impairment of primary cilia position and orientation.
The levels of the cell cycle phosphatase Cdc25A are controlled by proteolysis. A de-ubiquitylation enzyme, Dub3, stabilizes Cdc25A, is required for Cdc25A-mediated activation of Cdk1, and may contribute to oncogenic transformation by Cdc25A.
It remains unclear how proteins translocate across the peroxisomal membrane. Insights into a potential import pore are provided with the finding that the import receptor Pex5p forms a dynamic ion channel together with Pex14p, which can be induced to open upon receptor-cargo complex association.
Cells at the origin of tumour initiation are unknown for many cancers. In hedgehog-induced basal cell carcinoma, skin hair-follicle stem cells do not participate to tumorigenesis, whereas Hedgehog activation in stem cells from the interfollicular epidermis does induce malignancy.
A post-transcriptional pathway mediates TGFbeta-induced epithelial–mesenchymal transition (EMT). TGFβ-activated Akt phosphorylates the heterogeneous ribonucleoprotein E1, releasing it from the 3′-UTR of two transcripts required for EMT: disabled-2 (Dab2) and interleukin-like EMT inducer (ILEI).
The S phase kinase Cdc7-Dbf4 phosphorylates histone H3 at Thr 45 during DNA replication. Phosphorylation of histone H3 at this residue is important for normal replication.
PTP1B, an ER-localized tyrosine phosphatase, regulates signalling by various cell-surface receptors, including epidermal growth factor receptor (EGFR). Direct contacts between EGFR-containing endosomes and the ER allow EGFR and PTP1B to interact. PTP1B promotes sorting of EGFR into multivesicular bodies.
Notch-mediated transcriptional activation requires the formation of a ternary complex, consisting of NotchICD, CSL and a Mastermind family member. Nemo-like kinase is shown to negatively regulate Notch signalling and to promote neurogenesis in zebrafish by phosphoprylating Notch1ICD and reducing formation of the ternary complex.
Mouse node cilia are posteriorly tilted to generate a leftward fluid flow and left/right asymmetry in the embryo, but how the tilt comes about was not known. The basal bodies of node cilia gradually shift from a central position towards the posterior side of node cells in a dishevelled and non-canonical Wnt signalling-dependent manner and follow a shift in Dvl localization to the posterior.
The γ-tubulin ring complex (γ-TuRC) nucleates microtubules. The nuclear pore subcomplex Nup107-160 is found to interact and cooperate with γ-TuRC to nucleate microtubules at kinetochores, thereby promoting spindle assembly.
Whether cohesion-independent forces hold chromosomes together in metaphase is a debated issue. Artificial cleavage of cohesin is sufficient to induce chromosome disjunction in Drosophila syncytical embryos but cdk1 inactivation is required for normal subsequent chromosome separation.
The ATM signalling mediator proteins 53BP1 and KAP-1 are required for heterochromatic double-strand break DNA repair. 53BP1 aids Mre11, NBS1 and ATM accumulation at heterochromatic breaks, leading to localized phosphorylation of KAP-1 by ATM.